In continuation of efforts to develop a more effective narcotic antagonist for the prophylactic treatment of post-addicts against readdiction (a highly desirable alternative to methadone treatment), several new approaches will be studied. In previous work, eleven new substances in the morphinan and isomorphinan series have been prepared, and screening results on five of them have been obtained. The results are not uninteresting, but they do suggest that little improvement over the prototype isocyclorphan is likely to be obtained by simple elaboration of the isocyclorphan structure of the sort originally proposed. Accordingly, emphasis has been shifted to attempts to prepare analogs of the highly potent M5050 lacking the oxide bridge and further analogs with the ethano bridge across positions 5-8 rather than 6-14. These represent entirely new systems, but analogy suggests strongly that they should be potent and more long-acting than the prototype M-5050.